Nicolaou synthesis, apoptolidin

The total synthesis of apoptolidin was accomplished in the laboratory of K.C. Nicolaou. The key C12-C28 vinyl iodide fragment was prepared using the Schwartz hydrozirconation of an internal alkyne followed by trapping of the alkenylzirconium intermediate with iodine (I2). The vinyl iodide was formed as a 6 1 mixture of regioisomers. Under the reaction conditions, the methyl orthoester was converted to the methyl glycoside moiety at C21, which was presumably facilitated by the complexation of Zr with the pyranoside oxygen atom. 

This methodology was later applied by Nicolaou s group to the synthesis of a bromodieneoate intermediate required in the total synthesis of Apoptolidin (eq 72), and by Mladenova et al. for the synthesis of chloromethyltrienoic esters (eq 73). ... 

Successful total synthesis of apoptolidin A has been achieved by the groups of Nicolaou " " and Koert. " " Syntheses of apoptoUdinone A, its aglycon, were reported by the groups of Sulikowsky, Crimmins, Nico-laou, " " and Koert. " In addition, several studies on the synthesis of fragments of apoptoUdinones and analogs have been reported. " " ... 

SCHEME 38.41. Total synthesis of apoptolidin by Nicolaou et al. (part 1). 

Nicolaou KC, Li Y, Fylaktakidou KC, Mitchell HJ, Wei H-X, Weyershausen B. Total synthesis of apoptolidin part 1. Ret-rosynthetic analysis and construction of building blocks. Angew. Chem. Int. Ed. 2001 40 3849-3854. 

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